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Cited by 17Advancements in Transdermal Drug DeliverySkin and Cellular Biology ResearchDermatology and Skin Diseases

Characterization of human skin equivalents developed at body's core and surface temperatures

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Mieremet, Arnout, Dijk, Rianne, Boiten, Walter, Gooris, Gert, Bouwstra, Joke A., El Ghalbzouri, Abdoelwaheb·2019·Journal of Tissue Engineering and Regenerative Medicine
DOI 10.1002/term.2858PMC PMC6767576
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Abstract

Human skin equivalents (HSEs) are in vitro developed three-dimensional models resembling native human skin (NHS) to a high extent. However, the epidermal lipid biosynthesis, barrier lipid composition, and organization are altered, leading to an elevated diffusion rate of therapeutic molecules. The altered lipid barrier formation in HSEs may be induced by standardized culture conditions, including a culture temperature of 37°C, which is dissimilar to skin surface temperature. Therefore, we aim to determine the influence of culture temperature during the generation of full thickness models (FTMs) on epidermal morphogenesis and lipid barrier formation. For this purpose, FTMs were developed at conventional core temperature (37°C) or lower temperatures (35°C and 33°C) and evaluated over a time period of 4 weeks. The stratum corneum (SC) lipid composition was analysed using advanced liquid chromatography coupled to mass spectrometry analysis. Our results show that SC layers accumulated at a similar rate irrespective of culture temperature. At reduced culture temperature, an increased epidermal thickness, a disorganization of the lower epidermal cell layers, a delayed early differentiation, and an enlargement of granular cells were detected. Interestingly, melanogenesis was reduced at lower temperature. The ceramide subclass profile, chain length distribution, and level of unsaturated ceramides were similar in FTMs generated at 37°C and 35°C but changed when generated at 33°C, reducing the resemblance to NHS. Herein, we report that culture temperature affects epidermal morphogenesis substantially and to a lesser extent the lipid barrier formation, highlighting the importance of optimized external parameters during reconstruction of skin.

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  • HSEs can be completely submerged in medium for multiple days prior to raising them to an air-liquid interface to promote stratification, generated with immortalized keratinocyte cell lines, or seeded onto collagen layers.

    “HSEs can be completely submerged in medium for multiple days prior to raising them to an air-liquid interface to promote stratification,75 generated with immortalized keratinocyte cell lines,76 or seeded onto collagen layers.77”

    From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [77]

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Cited by

Sorted by citations

Authors
Mieremet, A., Dijk, R., Boiten, W., Gooris, G., Bouwstra, J. A., & El Ghalbzouri, A.
Affiliations
  • Leiden University (NL)
  • Research division BioTherapeutics, LACDR Leiden University Leiden The Netherlands
  • Department of Dermatology Leiden University Medical Centre Leiden The Netherlands
Corresponding author
Mieremet, Arnout
ORCID
Venue
Journal of Tissue Engineering and Regenerative Medicine
Publisher
Wiley
Published
2019-05-21
Volume
13
Issue
7
Pages
1122-1133
ISSN
  • 1932-6254 (ISSN-L)
  • 1932-7005
DOI
10.1002/term.2858
PMC
PMC6767576
OpenAlex
W2933464273
Cited by
17
References
1
Citations by year
2024: 2 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 3
FWCI
1.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Tissue Engineering and Regenerative Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
Stichting voor de Technische Wetenschappen (13151)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Keywords
human skin equivalents, culture temperature, epidermal morphogenesis, skin barrier formation, melanogenesis, epidermal differentiation, skin reconstruction
MeSH terms
Adult, Ceramides, Epidermis, Female, Humans, Models, Biological, Temperature, Keratinocytes, Lipid Metabolism

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